Essential Practical NMR for Organic Chemistry

Cover
Half Title
Essential Practical NMR for Organic Chemistry
Copyright
Dedication
Contents
Preface
1. Getting Started
	1.1 The Technique
	1.2 Instrumentation
		1.2.1 CW Systems
		1.2.2 FT Systems
		1.2.3 Probes
		1.2.4 Shims
	1.3 Origin of the Chemical Shift
	1.4 Origin of ‘Splitting’
	1.5 Integration
2. Preparing the Sample
	2.1 How Much Sample Do I Need?
	2.2 Solvent Selection
		2.2.1 Deutero Chloroform (CDCl3)
		2.2.2 Deutero Dimethyl Sulfoxide (DMSO)
		2.2.3 Deutero Methanol (CD3OD)
		2.2.4 Deutero Water (D2O)
		2.2.5 Deutero Benzene (C6D6)
		2.2.6 Carbon Tetrachloride (CCl4)
		2.2.7 Trifluoroacetic Acid (CF3COOH)
		2.2.8 Using Mixed Solvents
	2.3 Spectrum Referencing (Proton NMR)
	2.4 Sample Preparation
		2.4.1 Filtration
3. Spectrum Acquisition
	3.1 Number of Transients
	3.2 Number of Points
	3.3 Spectral Width
	3.4 Acquisition Time
	3.5 Pulse Width/Pulse Angle
	3.6 Relaxation Delay
	3.7 Number of Increments
	3.8 Non-Uniform Sampling (NUS)
	3.9 Shimming
	3.10 Tuning and Matching
	3.11 Frequency Lock
		3.11.1 Run Unlocked
		3.11.2 Internal Lock
		3.11.3 External Lock
	3.12 To Spin or Not to Spin?
4. Processing
	4.1 Introduction
	4.2 Zero-Filling and Linear Prediction
	4.3 Apodization
	4.4 Fourier Transformation
	4.5 Phase Correction
	4.6 Baseline Correction
	4.7 Integration
	4.8 Referencing
	4.9 Peak Picking
5. Interpreting Your Spectrum
	5.1 Common Solvents and Impurities
	5.2 Group 1 – Exchangeables and Aldehydes
	5.3 Group 2 – Aromatic and Heterocyclic Protons
		5.3.1 Monosubstituted Benzene Rings
		5.3.2 Multi-substituted Benzene Rings
		5.3.3 Heterocyclic Ring Systems (Unsaturated) and Polycyclic Aromatic Systems
	5.4 Group 3 – Double and Triple Bonds
	5.5 Group 4 – Alkyl Protons
6. Delving Deeper
	6.1 Chiral Centres
	6.2 Enantiotopic and Diastereotopic Protons
	6.3 Molecular Anisotropy
	6.4 Accidental Equivalence
	6.5 Restricted Rotation
	6.6 Heteronuclear Coupling
		6.6.1 Coupling between Protons and 13C
		6.6.2 Coupling between Protons and 19F
		6.6.3 Coupling between Protons and 31P
		6.6.4 Coupling between 1H and Other Heteroatoms
	6.7 Cyclic Compounds and the Karplus Curve
	6.8 Salts, Free Bases and Zwitterions
	6.9 Zwitterionic Compounds Are Worthy of Special Mention
7. Further Elucidation Techniques – Part 1
	7.1 Chemical Techniques
		7.1.1 Deuteration
		7.1.2 Basification and Acidification
		7.1.3 Changing Solvents
		7.1.4 Trifluoroacetylation
		7.1.5 Lanthanide Shift Reagents
		7.1.6 Chiral Resolving Agents
8. Further Elucidation Techniques – Part 2
	8.1 Introduction
	8.2 Spin-Decoupling (Homonuclear, 1-D)
	8.3 Correlated Spectroscopy (COSY)
	8.4 Total Correlation Spectroscopy (TOCSY) 1- and 2-D
	8.5 The Nuclear Overhauser Effect (NOE) and Associated Techniques
9. Carbon-13 NMR Spectroscopy
	9.1 General Principles and 1-D 13C
	9.2 2-D Proton–Carbon (Single Bond) Correlated Spectroscopy
	9.3 2-D Proton–Carbon (Multiple Bond) Correlated Spectroscopy
	9.4 Piecing It All Together
	9.5 Choosing the Right Tool
10. Nitrogen-15 NMR Spectroscopy
	10.1 Introduction
	10.2 Referencing
	10.3 Using 15N Data
	10.4 Amines
		10.4.1 Alkyl
		10.4.2 Aryl
	10.5 Conjugated Amines
	10.6 Amides
	10.7 Amidines
	10.8 Azides
	10.9 Carbamates
	10.10 Cyanates and Thiocyanates
	10.11 Diazo Compounds
	10.12 Formamides
	10.13 Hydrazines
	10.14 Hydroxamic Acids
	10.15 Hydroxylamines
	10.16 Imides (Alkyl and Aryl)
	10.17 Imines
	10.18 Isocyanates and Isothiocyanates
	10.19 Nitrogen-Bearing Heterocycles
	10.20 Nitriles
	10.21 Nitro Compounds
	10.22 Nitroso and N-Nitroso Compounds
	10.23 N-Oxides
	10.24 Oximes
	10.25 Sulfonamides
	10.26 Ureas and Thioureas
	10.27 Other Unusual Compounds
	10.28 15N Topics
		10.28.1 1-, 2-, 3- and 4-bond Correlations
		10.28.2 ‘Through-Space’ Correlations
		10.28.3 Tautomerism in 15N NMR
		10.28.4 Restricted Rotation
		10.28.5 Protonation and Zwitterions
11. Some Other Techniques and Nuclei
	11.1 HPLC-NMR
	11.2 Flow NMR
	11.3 Solvent Suppression
	11.4 MAS (Magic Angle Spinning) NMR
	11.5 Pure Shift NMR
	11.6 Other 2-D Techniques
		11.6.1 INADEQUATE
		11.6.2 J-Resolved
		11.6.3 DOSY
	11.7 3-D Techniques
	11.8 Fluorine (19F) NMR
	11.9 Phosphorus (31P) NMR
12. Dynamics
	12.1 Linewidths
	12.2 Chemical Shifts
	12.3 Splittings
	12.4 Relaxation Pathways
	12.5 Experimental Techniques
	12.6 In Practice
	12.7 In Conclusion
13. Quantification
	13.1 Introduction
	13.2 Different Approaches to Quantification
		13.2.1 Relative Quantification
		13.2.2 Absolute Quantification
		13.2.3 Internal Standards
		13.2.4 External Standards
		13.2.5 Electronic Reference (ERETIC)
		13.2.6 QUANTAS
		13.2.7 ERETIC2
	13.3 Things to Watch Out For
	13.4 Quantification of Other Nuclei
	13.5 Conclusion
14. Safety
	14.1 Magnetic Fields
	14.2 Cryogens
	14.3 Sample-Related Injuries
15. Software
	15.1 Acquisition Software
	15.2 Processing Software
	15.3 Prediction and Simulation Software
		15.3.1 13C Prediction
		15.3.2 1H Prediction
		15.3.3 Incremental Approaches
		15.3.4 HOSE Code Databases
		15.3.5 Semi-Empirical Approaches
		15.3.6 Ab Initio Approaches
		15.3.7 Neural Networks
		15.5.8 Hybrid Approaches
		15.5.9 Simulation
	15.6 Structural Verification Software
	15.7 Structural Elucidation Software
	15.8 Summary
16. Problems
	16.1 Questions
	16.2 Hints
	16.3 Answers
	16.4 A Closing Footnote
17. Raising Your Game
	17.1 Spotting the Pitfalls
	17.2 The Wrong Solvent
	17.3 Choosing the Right Experiment
Appendix A
Glossary
Index